Genetic Interference With Peroxisome Proliferator–Activated Receptor γ in Smooth Muscle Enhances Myogenic Tone in the Cerebrovasculature via A Rho Kinase–Dependent Mechanism
| العنوان: | Genetic Interference With Peroxisome Proliferator–Activated Receptor γ in Smooth Muscle Enhances Myogenic Tone in the Cerebrovasculature via A Rho Kinase–Dependent Mechanism |
|---|---|
| المؤلفون: | T. Michael De Silva, Frank M. Faraci, Curt D. Sigmund, Christopher J. Pelham, Pimonrat Ketsawatsomkron |
| المصدر: | Hypertension. 65:345-351 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | rho GTP-Binding Proteins, Middle Cerebral Artery, medicine.medical_specialty, RHOA, Cerebral arteries, Peroxisome proliferator-activated receptor, Sodium Chloride, Muscle, Smooth, Vascular, Article, Desoxycorticosterone Acetate, Mice, medicine.artery, Internal medicine, Internal Medicine, medicine, Animals, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, Rho-associated protein kinase, Protein kinase C, Genes, Dominant, Mice, Knockout, chemistry.chemical_classification, rho-Associated Kinases, biology, Gene Expression Profiling, Tetraethylammonium, PPAR gamma, Endocrinology, chemistry, Vasoconstriction, Rho kinase inhibitor, Cerebrovascular Circulation, Enzyme Induction, Hypertension, Middle cerebral artery, biology.protein, medicine.symptom, rhoA GTP-Binding Protein |
| الوصف: | Myogenic responses by resistance vessels are a key component of autoregulation in brain, thus playing a crucial role in regulating cerebral blood flow and protecting the blood–brain barrier against potentially detrimental elevations in blood pressure. Although cerebrovascular disease is often accompanied by alterations in myogenic responses, mechanisms that control these changes are poorly understood. Peroxisome proliferator–activated receptor γ has emerged as a regulator of vascular tone. We hypothesized that interference with peroxisome proliferator–activated receptor γ in smooth muscle would augment myogenic responses in cerebral arteries. We studied transgenic mice expressing a dominant-negative mutation in peroxisome proliferator–activated receptor γ selectively in smooth muscle (S-P467L) and nontransgenic littermates. Myogenic tone in middle cerebral arteries from S-P467L was elevated 3-fold when compared with nontransgenic littermates. Rho kinase is thought to play a major role in cerebrovascular disease. The Rho kinase inhibitor, Y-27632, abolished augmented myogenic tone in middle cerebral arteries from S-P467L mice. CN-03, which modifies RhoA making it constitutively active, elevated myogenic tone to ≈60% in both strains, via a Y-27632–dependent mechanism. Large conductance Ca 2+ -activated K + channels (BK Ca ) modulate myogenic tone. Inhibitors of BK Ca caused greater constriction in middle cerebral arteries from nontransgenic littermates when compared with S-P467L. Expression of RhoA or Rho kinase-I/II protein was similar in cerebral arteries from S-P467L mice. Overall, the data suggest that peroxisome proliferator–activated receptor γ in smooth muscle normally inhibits Rho kinase and promotes BK Ca function, thus influencing myogenic tone in resistance arteries in brain. These findings have implications for mechanisms that underlie large- and small-vessel disease in brain, as well as regulation of cerebral blood flow. |
| تدمد: | 1524-4563 0194-911X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20b834d1ff3e488c3247b39a186a55d5 https://doi.org/10.1161/hypertensionaha.114.04541 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....20b834d1ff3e488c3247b39a186a55d5 |
| قاعدة البيانات: | OpenAIRE |
كن أول من يترك تعليقا!